Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The N-myc downstream-regulated gene 2 (NDRG2) at 14q11.2 has been reported to be downregulated in glioblastoma, and NDRG2 overexpression represses glioblastoma cell proliferation in vitro (Deng et al., Int J Cancer 2003;106;342-7). To further address the role of NDRG2 as a candidate tumor suppressor in human gliomas, we analyzed 67 astrocytic tumors (10 diffuse astrocytomas, 11 anaplastic astrocytomas, 34 primary glioblastomas and 12 secondary glioblastomas) for NDRG2 gene mutation, promoter methylation and expression at the mRNA and protein levels. Using real-time reverse transcription PCR analysis, we found decreased NDRG2 mRNA levels in primary glioblastomas as compared to diffuse and anaplastic astrocytomas. Similarly, immunohistochemistry revealed low or absent NDRG2 protein expression in primary glioblastomas. Mutational analysis of the entire NDRG2 coding sequence did not reveal any tumor-associated DNA sequence alterations. However, sequencing of sodium bisulfite-modified DNA identified hypermethylation of the NDRG2 promoter region in 21 of 34 primary glioblastomas (62%). Moreover, NDRG2 promoter hypermethylation was associated with decreased NDRG2 mRNA expression. In contrast to primary glioblastomas, NDRG2 promoter hypermethylation was detected in only 1 of 11 anaplastic astrocytomas (9%) and was absent in 10 diffuse astrocytomas and 12 secondary glioblastomas. Taken together, our data support NDRG2 as a candidate tumor suppressor gene that is epigenetically silenced in the majority of primary glioblastomas, but not in lower grade astrocytomas and secondary glioblastomas.
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PMID:Frequent promoter hypermethylation and transcriptional downregulation of the NDRG2 gene at 14q11.2 in primary glioblastoma. 1870 45

NDRG2, a member of the N-Myc downstream-regulated gene family, was shown to be a putative tumor suppressor gene in glioblastoma and other cancers. Through a bioinformatic analysis, we found that NDRG2 protein contains an acyl carrier domain. In the current study, we therefore hypothesized that NDRG2 may play an important role in the regulation of histone acetylation. Treatment of U251 and U87 glioma cells with trichostatin A, an inhibitor of histone deacetylase, upregulated the expression of NDRG2 and acetylated forms of histones H3 and H4, reduced tumor cell viability and arrested the cell cycle at the G1/G0 phase. Overexpression of NDRG2 by transfecting glioma cells with adenovirus containing the NDRG2 gene upregulated the levels of acetylated forms of H3 and H4 whereas inhibition of NDRG2 expression by siRNA-mediated knockdown downregulated the level of histone acetylation. Furthermore, NDRG2 siRNA significantly reduced the level of histone acetylation induced by trichostatin A. Taken together, these data demonstrate that NDRG2 can regulate the level of histone acetylation to control glioma cell growth.
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PMID:Regulation of histone acetylation by NDRG2 in glioma cells. 2191 36